Stereotactic body radiation therapy (SBRT) has become an effective treatment paradigm for early stage non- small cell lung cancer (NSCLC) patients. The success of lung SBRT is determined by the accuracy of target localization as well as sparing of critical normal structures. Intrafraction verification is critical for lung SBRT due to its tight PTV margin, high fractional dse with small fraction number, and long treatment time. Purdie et al showed that lung tumor intrafraction motion increases with treatment time, and can be over 1cm for SBRT. Zhao et al reported a maximal drop of PTV coverage from 95% to 78% in lung SBRT using 5mm margin due to intrafraction motion. The accuracy of using kV fluoroscopy and MV cine imaging for intrafraction verification is limited especially for small tumors due to overlaying structures in 2 images. Conventional CBCT also has limited application for intrafraction verification due to large scanning angle, long acquisition time, high imaging dose and limited mechanical clearance. By far, neither 3D nor 4D volumetric x-ray imaging techniques are available for target verification on-the-fly during actual treatment delivery. This research plan proposes to develop a Limited-angle Intrafraction Verification (LIVE) system for fast 4D verification during arc treatment delivery or in between 3D/IMRT beams. The long term goal of the LIVE system is to improve the tumor control and reduce normal tissue toxicity for lung SBRT by substantially reducing the treatment errors caused by intrafraction motion and improving the accuracy of ART. The specific aims of the proposal are: 1) Build the LIVE system by developing novel image acquisition, sorting, kV-MV aggregation and reconstruction techniques. 2) Optimize the accuracy, efficiency and imaging dose of LIVE through respiratory motion modeling, novel acceleration strategies, and XCAT and Monte Carlo (MC) simulation. 3) Evaluate the LIVE system for IGRT and ART. LIVE creatively combined a number of new technologies being developed for fast intrafraction verification: 1) limited-angle kV-MV image acquisition; 2) automatic projection sorting based on Fourier Transformation of projections; 3) kV-MV aggregation using linear fitting, virtual mono-energetic and dual CT techniques; 4) 4D- and phase-matched digital tomosynthesis (DTS) and prior knowledge based CBCT reconstruction methods; 5) respiratory motion modeling; 6) adaptive reconstruction strategy; and 7) new acceleration strategies. Parameters of the LIVE system, including beam energy, fluence, kV-MV imaging sequence, number of kV-MV projections, and scan angle will be optimized for different tumor sizes and locations through 4D digital extended cardiac-torso phantom (XCAT) and Monte Carlo (MC) simulation. MC will also be used to evaluate the imaging dose. The effectiveness of LIVE system for IGRT and ART applications will be quantitatively evaluated through phantom studies using the CIRS dynamic thorax motion phantom and patient studies using lung patient CBCT and MV cine image data collected in a retrospective study.